Insulin resistance: still an underestimated factor in polycystic ovary syndrome?


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VOLUME 115, ISSUE 6, P1447-1448


Anna Lena Zippl, M.D., Beata Seeber, M.D., Ludwig Wildt, M.D., Ph.D.


Reflections on "Menstrual dysfunction in polycystic ovary syndrome: association with dynamic state insulin resistance rather than hyperandrogenism" by Ezeh et al.

Read the full text here. 

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. 


Go to the profile of Pandiyan  Natarajan
6 months ago

Insulin Resistance and PCOS.

We read with considerable interest the Reflections on Insulin Resistance in PCOS.

Insulin Resistance has been implicated in the etiopathology of  PCOS, Type 2 Diabetes Mellitus and the Metabolic syndrome, Fatty Liver and Coronary artery disease. The precise mechanism by which Insulin Resistance leads to all these clinical conditions is not clear. Insulin levels are variable in all these patients and do not correlate with the clinical condition.

Insulin Resistance is a nebulous entity and is not used in routine clinical practice in the management of PCOS, Type 2 Diabetes Mellitus or Metabolic syndrome. The inconvenient truth about Insulin Resistance seems to be that the so called Insulin Resistance may well be the consequence of Hyperglycemia and not the cause of it. (1 )

PCOS is primarily due to Abnormal weight gain in adolescence or adult life. Most of the patients with PCOS are either overweight or obese. The few who are so called normal weight or thin also seemed to have gained significant weight in adulthood though they may still be in the normal weight or thin weight range. ( 2 )

Weight loss by modification of diet and exercise seems to be the Only logical step in the management of PCOS, Type 2 Diabetes Mellitus and Metabolic syndrome. Drugs for Induction of Ovulation in infertile PCOS patients should be the second line of management. Metabolic surgery and burning of the ovaries by Laparoscopic Endocautery of the ovaries would be futile and can cause more harm than good. 

Insulin estimation will not yield any useful information and will cause more confusion than clarity. We reiterate that the primary focus should be on weight loss.

 1) Anand Chockalingam, Pandiyan Natarajan, Puvithra Thanikachalam, Radha Pandiyan.

Insulin Resistance: The Inconvenient Truth. 

Missouri Medicine 2021; 118:2; 119.

2) Puvithra T, Pandiyan N.

Is weight gain the Precipitating Factor for Polycystic Ovarian Syndrome? A Hypothesis Based on Retrospective Study.

Chettinad Health City Medical Journal 2015; 4;3; 120-124.

Professor Dr Pandiyan Natarajan,

Professor and Head of the Department of Andrology and Reproductive Medicine.

Chettinad Super Speciality Hospital,

Chettinad Academy of Research and Education,

Tamil Nadu,

India- 603103.

Go to the profile of Erika P. New
6 months ago

An interesting discussion. The group of PCOS patients who are normal weight have always been of interest to me. In my experience, the normal weight PCOS patients have not gained significant weight in adulthood. This phenotype of PCOS is likely related to the metabolic factors such as insulin resistance as are discussed in the reflection. But with the tests for insulin resistance not being very practical in reality, maybe the take away is to remember to counsel all PCOS patients, not just those who are overweight or obese, on healthy diet and lifestyle. Many may already do this, but I definitely think it is more in the forefront of our minds when our patients are overweight or obese.

Go to the profile of Pandiyan  Natarajan
5 months ago

Insulin Resistance- The Inconvenient Truth.

Thank you very much for your Reflections and thoughtful Response to our comments. The first symptom of abnormal weight gain in a woman is irregularities of menstrual cycle which may progress to Anovulation and PCOS.

In our experience in almost all women with PCOS, there has been significant weight gain in adult life. In an unpublished series of 143 women, 2 women were even thin and many had normal BMI. But, all these women have had significant weight gain in adult life, though many had BMIs still in the normal range and 2 of these women were even considered thin.

The BMI we use is the population average. For the individual what matters is her weight at menarche, adolescent weight and adult weight. We have also observed that women gain weight at puberty which is of course physiological. Post pubertal weight gain occurs when they enter college and again after marriage, all of which predisposes to PCOS.

We now believe that PCOS is an Epiphenomenon.(1 )

Insulin Resistance is a hypothetical concept, not used in clinical practice. The Inconvenient Truth is, it is not the cause of PCOS, Type 2 Diabetes Mellitus or the Metabolic syndrome. It is the consequence. There is no resistance to Insulin action in these patients ( 2 ). 

The term PCOS itself, in our opinion is a misnomer. The ovary is Poly Follicular and not Poly cystic. By convention, we continue to use the term PCOS.

1)  Puvithra.T, N.Pandiyan. Polycystic Ovary Syndrome is an Epiphenomenon - An Opinion.

Chettinad Health City Medical Journal 2016; 5(3): 106 - 107

2) Anand Chockalingam, Pandiyan Natarajan, Puvithra Thanikachalam, Radha Pandiyan.

Insulin Resistance: The Inconvenient Truth. 

Missouri Medicine 2021; 118:2; 119.